Percodan was reformulated in 2005; prior to 2005, it contained two oxycodone salts—4.62 mg of oxycodone hydrochloride and 0.38 mg of oxycodone terephthalate. Since the latter salt is unusual in the pharmacopeia, the manufacturer increased the amount of oxycodone hydrochloride to 4.8355 and discontinued the oxycodone terephthalate.

Percodan has largely been replaced by Percocet (which is a compound of oxycodone and paracetamol, instead of Percodan's aspirin) and other oxycodone-containing compounds for post-operative pain, since aspirin and other anti-inflammatory drugs increase prothrombin time and thus inhibit the blood from clotting, which can result in post-operative complications, such as excessive bleeding. Norco and Vicodin, which contain hydrocodone and paracetamol, have also gained favor over Percodan for post-operative pain because hydrocodone is nearly as potent as oxycodone, and it is not as highly regulated. In the United States, Percodan is regulated as a Schedule II controlled substance under the Uniform Controlled Substances Act of 1970, along with cocaine, morphine and raw (unprocessed) opium. Schedule II prescriptions may not be filled by telephone (except in an emergency), and no refills are allowed. As of October 6th 2014, Vicodin, Norco, and other hydrocodone-containing compounds are NOW SCHEDULE II. Percodan is becoming something of a relic in the United States, at least, as the number of prescriptions has fallen precipitously since the 1960s in light of the alternate drugs available containing oxycodone (Percocet, Tylox, OxyContin, Roxicodone).

The combination oxycodone/aspirin is also sold under the brand name Endodan. All products containing oxycodone (including Percodan, Percocet, OxyContin) have the potential to be habit-forming. Oxycodone can produce drugdependence of the morphine type and, therefore, has the potential for being addictive.